Journal of the Neurological Sciences最新文献

{"title":"Low synaptic and neurosecretory proteins in cerebrospinal fluid in early parkinsonian disease","authors":"Protik Jakobsson ,&nbsp;Johanna Nilsson ,&nbsp;Maria Nygren ,&nbsp;Henrik Zetterberg ,&nbsp;Kaj Blennow ,&nbsp;Radu Constantinescu ,&nbsp;Julius Constantinescu ,&nbsp;Ann Brinkmalm ,&nbsp;David Bäckström","doi":"10.1016/j.jns.2025.123683","DOIUrl":"10.1016/j.jns.2025.123683","url":null,"abstract":"<div><h3>Background</h3><div>The early pathogenesis of Parkinson's disease (PD) and the atypical parkinsonian disorders multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) is poorly understood, but presynaptic and axonal dysfunction are hypothesized to play a prominent role.</div></div><div><h3>Objective</h3><div>To identify synapse- and/or axonal dysfunction as indicated by cerebrospinal fluid (CSF) biomarker profiles and their clinical correlates in early-stage PD, MSA, and PSP.</div></div><div><h3>Methods</h3><div>Liquid chromatography mass spectrometry and enzyme-linked immunosorbent assay analyses of CSF samples from patients with early-stage PD (<em>n</em> = 38), MSA (<em>n</em> = 21), or PSP (<em>n</em> = 19), and age-matched, neurologically healthy controls (<em>n</em> = 30).</div></div><div><h3>Results</h3><div>Compared to controls, patients with early parkinsonian disorders had significantly reduced CSF levels of the synapse-associated proteins neuronal pentraxin-1 (NPTX1), amyloid precursor protein, and β-amyloid 42 (Aβ42), as well as the neurosecretory granin-derived proteins secretogranin-II, chromogranin-A, and secretogranin-VII. Among these, synapse-associated proteins correlated with non-motor features, while none correlated with age. CSF levels of the predominantly axonal proteins neurofilament light (NfL) and tau were elevated in patients with MSA or PSP. Reduced NPTX1 and Aβ42 distinguished PD from PSP, while elevated NfL and tau distinguished PSP and/or MSA from PD.</div></div><div><h3>Conclusions</h3><div>Low CSF levels of biomarkers associated with synaptic and neurosecretory function (e.g., NPTX1) implicate age-independent synaptic dysfunction as a shared, early feature in the pathogenesis of PD, MSA, and PSP. Such biomarkers may be particularly sensitive correlates of early non-motor dysfunction. Early axonal dysfunction is more pronounced in PSP and MSA than in PD.</div></div>","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":"478 ","pages":"Article 123683"},"PeriodicalIF":3.2,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving prognostic models of six-month clinical outcomes after severe traumatic brain injury with daily inpatient biomarkers: A Bayesian modelling approach","authors":"Shawn R. Eagle ,&nbsp;Regan Shanahan ,&nbsp;Jaeyong Shim ,&nbsp;Anna Slingerland ,&nbsp;Shovan Bhatia ,&nbsp;Michael R. Kann ,&nbsp;Tyler Augi ,&nbsp;Ava Puccio ,&nbsp;David O. Okonkwo","doi":"10.1016/j.jns.2025.123682","DOIUrl":"10.1016/j.jns.2025.123682","url":null,"abstract":"<div><h3>Background</h3><div>A key limitation of the IMPACT model for prognostication after severe traumatic brain injury (TBI) is the use of predictors from hospital admission only. We sought to identify if including daily blood labs (e.g., glucose, sodium, platelets, hemoglobin) and other vitals (e.g., heart rate, mean arterial pressure [MAP], partial pressure of carbon dioxide [PaCO2]) for the first 2 weeks post-severe TBI improves prognostication compared to the IMPACT model alone.</div></div><div><h3>Methods</h3><div>This is a secondary analysis of a prospectively collected database of patients from a single level 1 trauma center between November 2002 and December 2018 (<em>n</em> = 315). All patients had severe TBI at presentation, defined as Glasgow Coma Scale (GCS) ≤8. Researchers extracted daily blood labs and vitals for the first 14 days post-injury. We used Naïve Bayes to estimate class-conditional probabilities for an “IMPACT-only” model and a “full” model with the IMPACT score plus the biomarkers measured on post-injury days 1–13. The top ten predictors were included in the full model. DeLong's test assessed whether the difference in area under the curve (AUC) were significant (<em>p</em> &lt; 0.05).</div></div><div><h3>Results</h3><div>The full model to predict unfavorable outcomes at six-months had significantly better discrimination (AUC = 0.83) compared to the IMPACT model (AUC = 0.74; <em>p</em> &lt; 0.01). The full model to predict death by six-months had significantly better discrimination (AUC = 0.83) compared to the IMPACT model (AUC = 0.75; <em>p</em> = 0.02).</div></div><div><h3>Conclusions</h3><div>Biomarkers typically collected as part of inpatient clinical workups over the first two weeks post-injury improved discrimination of unfavorable outcomes and mortality by six-months compared to IMPACT.</div></div>","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":"478 ","pages":"Article 123682"},"PeriodicalIF":3.2,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144989735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic and clinical profile of a Brazilian cohort of dopa-responsive dystonia","authors":"Agostinho de Alencar Guerra ,&nbsp;Eduardo Boiteux Uchoa Cavalcanti ,&nbsp;Vinicius Viana Abreu Montanaro ,&nbsp;Thiago Falcao Hora ,&nbsp;Daniel Rocha de Carvalho ,&nbsp;Adriana Gonçalves da Silva ,&nbsp;Alessandra De La Rocque Ferreira ,&nbsp;Felipe von Glehn","doi":"10.1016/j.jns.2025.123680","DOIUrl":"10.1016/j.jns.2025.123680","url":null,"abstract":"<div><h3>Background</h3><div>Dopa-responsive dystonia (DRD) is a rare genetic and neurotransmitter disorder also known as Segawa Disease. The guanosine triphosphate cyclohydrolase 1 (<em>GCH1)</em> gene variants, inherited in an autosomal dominant pattern, are the most common cause of DRD.</div></div><div><h3>Objectives</h3><div>To describe the genetic and clinical profile of a Brazilian cohort of DRD patients.</div></div><div><h3>Methods</h3><div>Twenty-two patients were recruited from the SARAH Network of Rehabilitation Hospitals. A retrospective analysis of phenotype-genotype correlation from the next generation sequencing (NGS) genetic test alongside clinical features and evolution were performed. Clinical measures included: age at the disease onset, gender, time of diagnosis, response to Levodopa medication, behavioral symptoms related to psychiatric disorders.</div></div><div><h3>Results</h3><div>Variants in genes associated with DRD were detected in 17 patients (77 %), of which 16 (94 %) presented variants in the <em>GCH1</em> gene (pathogenic variants, <em>n</em> = 10; likely pathogenic variants, <em>n</em> = 6) and, 1 (5 %) in the tyrosine hydroxylase (TH) gene. The average age at disease onset was 7.8 years, with a predominant diagnosis in females, accompanied by a significant delay. A moderate positive response to a low dosage of Levodopa was observed. Patients also reported severe behavioral symptoms related to psychiatric disorders and use of medication.</div></div><div><h3>Conclusions</h3><div>The autosomal dominant <em>DYT/PARK-GCH1</em> was the most prevalent subtype. Not all patients were characterized with typical phenotypes contributing to the significant diagnosis delay. Uncommon occurrences of behavioral symptoms and Levodopa-induced dyskinesias were also found. Particular attention is suggested to the autosomal recessive form of the <em>GCH1</em>.</div></div>","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":"478 ","pages":"Article 123680"},"PeriodicalIF":3.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145020371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electronic health record analysis reveals no association between COVID-19 vaccines and ischemic stroke","authors":"Steve R. Makkar ,&nbsp;Kristen Hansen ,&nbsp;Nathan Hotaling ,&nbsp;Hythem Sidky ,&nbsp;on behalf of the N3C Consortium","doi":"10.1016/j.jns.2025.123681","DOIUrl":"10.1016/j.jns.2025.123681","url":null,"abstract":"<div><h3>Background</h3><div>We aimed to conduct a comprehensive investigation of the association between COVID-19 vaccination and incident ischemic stroke.</div></div><div><h3>Methods</h3><div>Using data from the National COVID Cohort Collaborative (N3C) database, we identified 119,275 patients (<em>n</em> = 39,922 vaccinated, <em>n</em> = 79,353 unvaccinated) who were at least 16 years of age and suffered ischemic stroke between February 2021 and April 2023. We applied the Self-Controlled Case Series (SCCS) to estimate the association between multiple vaccine-type-dose combinations and risk of incident ischemic stroke. We calculated incident rate ratios (IRRs) to compare incidence of ischemic stroke during the 28-day risk period following vaccine or SARS-CoV-2 exposure versus baseline periods of no vaccine exposure. Because patients who experience strokes are unlikely to receive the first or subsequent vaccinations, we applied SCCS methods capable of handling such event-dependent exposure to ensure valid results.</div></div><div><h3>Results</h3><div>Using the SCCS method robust to event-dependent exposures, no associations between any of the vaccine exposures and incident ischemic stroke were found. When we applied the standard SCCS, however, relative to baseline, there was elevated risk of incident ischemic stroke following first doses of BNT162b2 (IRR = 1.42, 95 % CI: 1.24–1.62), mRNA1273 (IRR =1.37, 95 % CI: 1.16–1.62), and Ad26.COV2·S (IRR = 1.40, 95 % CI: 1.08–1.81) vaccine types. No significant results emerged for the Bivalent vaccines. Effect sizes were larger in patients vaccinated once versus multiple times, implying ischemic stroke incidence likely prevented patients receiving initial and/or subsequent vaccinations.</div></div><div><h3>Conclusions</h3><div>Results indicate no association between mRNA or adenovirus COVID-19 vaccines and ischemic stroke.</div></div>","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":"478 ","pages":"Article 123681"},"PeriodicalIF":3.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obituary Robert Barry Daroff","authors":"Vladimir Hachinski ,&nbsp;Raad Shakir","doi":"10.1016/j.jns.2025.123674","DOIUrl":"10.1016/j.jns.2025.123674","url":null,"abstract":"","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":"478 ","pages":"Article 123674"},"PeriodicalIF":3.2,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145060871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rethinking folic acid fortification","authors":"Edward H. Reynolds","doi":"10.1016/j.jns.2025.123677","DOIUrl":"10.1016/j.jns.2025.123677","url":null,"abstract":"","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":"477 ","pages":"Article 123677"},"PeriodicalIF":3.2,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144958977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rethinking folic acid fortification: A call for nuanced strategies and broader investigations","authors":"Junlong Chen ,&nbsp;Jialin Liu","doi":"10.1016/j.jns.2025.123678","DOIUrl":"10.1016/j.jns.2025.123678","url":null,"abstract":"<div><div>This comment letter responds to Edward H. Reynolds' comprehensive review on folate, vitamin B12, one‑carbon metabolism, and nervous system health. While commending the review's insights into the potential neurological harms of excess folic acid, especially with vitamin B12 deficiency, we expand on several critical areas. We emphasize distinguishing synthetic folic acid's neurotoxicity from natural folates, urging further comparative studies. We highlight the underexplored long-term consequences of supraphysiological folic acid exposure in children and adolescents during critical neurodevelopment. The profound implications of transgenerational epigenetic effects from ancestral folate status are stressed, demanding urgent investigation in human cohorts. Crucially, we address the practical challenges of revising global fortification policies, noting the significant logistical, economic, and regulatory hurdles in shifting from folic acid to natural folate forms combined with vitamin B12. We conclude by advocating for a nuanced, multi-pronged approach to fortification, urging reconsideration of the folic acid UL, enhanced population surveillance, and continued research to balance benefits of neural tube defect prevention with potential harms of excess folate.</div></div>","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":"477 ","pages":"Article 123678"},"PeriodicalIF":3.2,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144958925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum neurofilament light chain levels are associated with cognitive decline in a consecutive cohort of patients with Alzheimer's disease.","authors":"C.S. Musaeus ,&nbsp;H.S. Gleerup ,&nbsp;F.K. Clemmensen ,&nbsp;F. Sellebjerg ,&nbsp;M.B. Hansen ,&nbsp;H.B. Søndergaard ,&nbsp;G. Waldemar ,&nbsp;S.G. Hasselbalch ,&nbsp;A.H. Simonsen","doi":"10.1016/j.jns.2025.123679","DOIUrl":"10.1016/j.jns.2025.123679","url":null,"abstract":"<div><h3>Background</h3><div>Alzheimer's disease (AD) is characterized by cognitive decline, but the individual progression rates vary. One type of blood-based biomarker that has been widely investigated is neurofilament light chain (NfL), as it reflects measures neuronal damage.</div></div><div><h3>Aim</h3><div>The aim of the current study was to investigate whether NfL could determine the rate of progression in patients with AD.</div></div><div><h3>Methods</h3><div>A total of 274 patients with dementia due to AD in the mild to moderate stage were included in the study, during the initial diagnostic evaluation at a memory clinic. At the initial evaluation, blood samples were collected, and the serum was analyzed for NfL. Follow-up by a clinician was performed in accordance with the workflow in the clinic.</div></div><div><h3>Results</h3><div>A significant negative association was found between short-term progression (days, mean (SD): 365 ± 224) and NfL (estimate (log-transformed): −1.2792, <em>p</em>-value: 0.003). No significant association was found between long-term progression (days, mean (SD): 611 (323) and NfL. NfL could not separate whether a patient was going to progress more than two points on the Mini-Mental Status Examination (MMSE) between the baseline visit and the first follow-up.</div></div><div><h3>Conclusions</h3><div>Although serum levels of NfL were associated with changes in MMSE, they do not alone provide sufficient utility for long term monitoring of cognitive decline in patients with AD. To achieve the desired sensitivity for this purpose, a combination of blood-based biomarkers, validated in clinical cohorts, may be necessary.</div></div><div><h3>Significance statement</h3><div>This study suggests that serum levels of neurofilament light chain cannot predict cognitive decline in individual patients with Alzheimer's Disease.</div></div>","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":"477 ","pages":"Article 123679"},"PeriodicalIF":3.2,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144922463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to letter to the editor: “Preliminary analysis of the association between apolipoprotein E genotype, amyloid burden, and cognitive decline in non-demented Parkinson's disease patients”","authors":"Clara Trompeta ,&nbsp;Beatriz Fernández-Rodríguez ,&nbsp;Roberto Fernández-Fernández ,&nbsp;Carmen Gasca-Salas","doi":"10.1016/j.jns.2025.123676","DOIUrl":"10.1016/j.jns.2025.123676","url":null,"abstract":"","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":"477 ","pages":"Article 123676"},"PeriodicalIF":3.2,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144922528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the editor – “Preliminary analysis of the association between apolipoprotein E genotype, amyloid burden, and cognitive decline in non-demented Parkinson's disease patients”","authors":"Wenwen Xu,&nbsp;Guoxin Zhang","doi":"10.1016/j.jns.2025.123675","DOIUrl":"10.1016/j.jns.2025.123675","url":null,"abstract":"","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":"478 ","pages":"Article 123675"},"PeriodicalIF":3.2,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}